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Effect of aluminium chloride on metabolism of 4-nitroquinoline 1-oxide
Abstract:
Aluminium chloride was subcutaneously administered to mice and its effect on the activities of 4-nitroquinoline 1-oxide (4-NQO) reductase and 4-hydroxyaminoquinoline 1-oxide (4-HAQO) reductase, and the organ distribution of carcinogen(s) in mouse lung and liver were examined. Subcutaneous administration of aluminium chloride in mice results in significant elevation of 4-NQO reductase and 4-HAQO reductase activities in their lung and liver, compared with those of the control. Simultaneous subcutaneous administration of aluminium chloride with 4-nitroquinoline[5, 6, 7, 8, 9, 10-14C] 1-oxide (14C-4-NQO) and examination of radioactivity distribution in the lung and liver showed that the radioactivity per tissue, 0.5 and 1 hr after the administration, decreased in the lung but inversely increased in the liver. Radioactivity in the lung and liver 2 hr after the administration was not different from that of the control. Simultaneous subcutaneous administration of 14C-4-NQO and aluminium chloride resulted in decreased distribution of 4-NQO and 4-HAQO in the lung compared with that of the control, while the distribution of their metabolites, 4-aminoquinoline 1-oxide (4-AQO) and 4-hydroxyquinoline 1-oxide (4-OHQO), inversely increased. Distribution of 4-aminoquinoline (4-AQ) and 4-hydroxyquinoline (4-OHQ) in the lung was not different from that of the control. These results suggest that the rapid metabolic changes of carcinogenic 4-NQO and 4-HAQO to noncarcinogenic substance(s) and decrease in the concentration of carcinogenic substances in the lung by the subcutaneous administration of aluminium chloride constitutes one of the factors for the mechanism of the suppression of carcinogenesis by aluminium chloride.
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